{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:45Z","timestamp":1753861785694,"version":"3.41.2"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Capillary malformation\u2010arteriovenous malformation (CM\u2010AVM) syndrome is characterized by the presence of multiple small (1\u20132\u2009cm in diameter) capillary malformations of the skin. This disorder has been described as two distinct entities: CM\u2010AVM1 and CM\u2010AVM2. The diagnosis of these disorders has been associated with pathogenic variants in the <jats:italic>RASA1<\/jats:italic> gene for <jats:italic>RASA1<\/jats:italic>\u2010CM\u2010AVM, formerly known as CM\u2010AVM1, and, more recently, the <jats:italic>EPHB4<\/jats:italic> genes for <jats:italic>EPHB4<\/jats:italic>\u2010CM\u2010AVM, formerly known as CM\u2010AVM2. Affected patients with either type may also have arteriovenous malformations and fistulas, which can cause life\u2010threatening bleeding, congestive heart failure, or neurologic consequences such as stroke. These syndromes are typically either sporadic or inherited in an autosomal dominant manner with variable expressivity. We report a case series of a father and three daughters who have clinically diagnosed <jats:italic>EPHB4<\/jats:italic>\u2010CM\u2010AVM syndrome who were found to have a variant of uncertain significance (VUS) in <jats:italic>EPHB4<\/jats:italic> that has only been reported once prior.<\/jats:p>","DOI":"10.1002\/ajmg.a.63898","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T13:08:52Z","timestamp":1729516132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Second Report of the <scp>p.Leu874Pro<\/scp> Missense Variant\u00a0in\u00a0<scp><i>EPHB4<\/i><\/scp> in a Family With Capillary Malformation\u2010Arteriovenous Malformation Syndrome (<scp>CM<\/scp>\u2010<scp>AVM<\/scp>) Syndrome"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-292X","authenticated-orcid":false,"given":"Laura E.","family":"Goeser","sequence":"first","affiliation":[{"name":"Department of Dermatology Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-8649","authenticated-orcid":false,"given":"Leah","family":"Lalor","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Division of Pediatric Dermatology, and Pediatrics, Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-2718","authenticated-orcid":false,"given":"Yvonne E.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Division of Pediatric Dermatology, and Pediatrics, Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0386-7622","authenticated-orcid":false,"given":"Michael","family":"Muriello","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetics Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.026886"},{"volume-title":"GeneReviews\u00ae [Internet]","year":"1993","author":"Bayrak\u2010Toydemir P.","key":"e_1_2_8_3_1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2340\/actadv.v102.1126"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200817"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.10.004"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.12112"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22431"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/JOVA.0000000000000052"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1907"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16326"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.14428"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100443\u2010z"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:16:26Z","timestamp":1748348186000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,21]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/ajmg.a.63898"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63898","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2024,10,21]]},"assertion":[{"value":"2024-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63898"}}